Ramosetron is called (−)-(R)-5-[(1-methyl-1H-indol-3-yl)carbonyl]-4,5,6,7-tetrahydro-1H-benzimidazolein its chemical name.
Ramosetron hydrochloride has been sold as an agent for improving the gastrointestinal symptoms (nausea and vomiting) associated with anticancer drug therapy (such as cisplatin) and it is usually administered to adults either orally at 0.1 mg once daily or intravenously at 0.3 mg once daily (“Nasea OD Tablet 0.1 mg”, “Nasea Injections 0.3 mg” in JAPAN PHARMACEUTICAL REFERENCE, PRODUCTS and ADMINISTRATION in JAPAN, The Fifth Edition (1999) published by the Japan Medical Products International Trade Association).
In EP-A-381422, there is a disclosure that a series of tetrahydrobenzimidazole derivatives including ramosetron and pharmaceutically acceptable salts thereof has an antagonistic action to 5HT3 receptors. On the basis of such an action, there is suggested a possibility of suppression of emesis caused by anti-cancer drugs such as cisplatin and radioactive ray and prevention and treatment of migraine, complex headache, trigeminal neuralgia, anxiety symptom, gastrointestinal motility abnormalities, peptic ulcer, irritable bowel syndrome, etc. and there is a description that usual clinical dose per day for adults is 0.1 to 10 mg by intravenous injection and 0.5 to 50 mg by oral administration which is administered once daily or by dividing into several times.
On the other hand, in WO 99/17755, there is a description that 5HT3 receptors are useful for the treatment of female patients suffering from non-constipated irritable bowel syndrome and that the therapeutically effective dose is within a range of 0.01 to 500 mg or, preferably, 0.05 to 50 mg per day. To be more specific, as a result of clinical study where 1 to 8 mg of alosetron were administered twice daily to the patients suffering from non-constipated irritable bowel syndrome, significant improvement was noted in female patients as compared with placebo in relief of pain and discomfort, stool consistency, bowel movement frequency and the proportion of days with urgency treatment while, in male patients, no significant improvement was noted as compared with placebo except stool consistency.
In addition, in WO 2002/007713, there is a description that, when 1 to 16 mg of 5HT3 receptor antagonist are administered three times a day, that is useful for the treatment of irritable bowel syndrome in both male and female patients.